In 1942 Albright and his associates described the features of a new clinical syndrome "pseudohypoparathyroidism." Patients with this disorder differ from those with idiopathic hypoparathyroidism in that they have characteristic constitutional features and they do not respond to exogenous parathyroid extract. Our findings that parathyroid hormone action is likely mediated through activation of adenylate cyclase, led us to test cases of pseudohypoparathyroidism by giving intravenous parathyroid hormone and measuring cyclic 3', 5' -AMP in the urine. In normal subjects as well as usual forms of hypoparathyroidism, parathyroid hormone causes a 10- to 60-fold increase in urinary cyclic AMP (cAMP). This response is abnormal (slight or no increased cAMP excretion) in pseudohypoparathyroidism, indicating that there is a defective parathyroid hormone-adenylate cyclase complex in the kidney in this disorder.